Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease

Alessandro Armuzzi, Giovanni Monteleone, Markus F. Neurath, Sandro Ardizzone, Antonio Di Sabatino, Massimo C. Fantini, Fabiana Castiglione, Maria L. Scribano, Flavio Caprioli, Giacomo C. Sturniolo, Francesca Rogai, Maurizio Vecchi, Raja Atreya, Fabrizio Bossa, Sara Onali, Maria Fichera, Gino R. Corazza, Livia Biancone, Vincenzo Savarino, Roberta PicaAmbrogio Orlando, Francesco Pallone

Research output: Contribution to journalArticle

263 Citations (Scopus)


Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7. In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28. The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P<0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P=0.04, P<0.001, and P<0.001, respectively). Most adverse events were related to complications and symptoms of Crohn's disease. We found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo.
Original languageEnglish
Pages (from-to)1104-1113
Number of pages10
JournalNew England Journal of Medicine
Publication statusPublished - 2015


  • Crohn's disease
  • SMAD7 antisense oligonucleotide


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